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The motion of ferroelectric domain walls is critical in determining the response of ferroelectrics to an applied stimulus. Here, the authors directly measure the effect of an additional non-motional or stationary domain wall contribution to dielectric susceptibility in nanodomain ferroelectric films.

Adaptation of Mycobacterium tuberculosis to the host environment is principally mediated through its transcription factors. Here, the authors report the DNA binding and transcriptional profile of ~80% of all predicted M. tuberculosistranscription factors, and find wide-spread dormant DNA binding.

A non-genetic mechanism of sex determination in the human malaria parasite, Plasmodium falciparum, is described, and the male development 1 gene is identified as a potential target for interventions that block malaria transmission.

Light-Seq uses light-directed DNA barcoding in fixed cells and tissues for multiplexed spatial indexing and subsequent next generation sequencing. This approach blends spatial and omics information to enable analysis of rare cell types in complex tissues.

Analysis of chromatin state and accessibility in mouse tissues from twelve sites and eight developmental stages provides a comprehensive view of chromatin dynamics.

Controlling the self-assembly of large coordination cages is challenging owing to entropic costs and difficulties in error correction. Now an array of large cages prepared by the rational design of alterations that allow for the tuning of the dihedral angle between pentagonal subunits is reported.

Mosses are a highly diverse lineage of land plants. Here, the authors provide a detailed phylogeny of 29 orders of moss, using nuclear and organelle data to provide robust hypotheses for most of the ordinal moss relationships.

A mouse model of gliomagenesis reveals that olfaction can directly regulate the genesis of gliomas, showing that sensory experience and gliomagenesis are linked and providing insight into the neural circuitry involved.

Here, the authors demonstrate that a secondary electron electron-beam-induced current imaging technique in a scanning transmission electron microscope can be applied to spatially resolve the atomic scale electron density in an encapsulated WSe₂ monolayer.

Last year the first map of single nucleotide changes was published; now an international consortium has mapped even larger areas of differences, called copy number variants. These variants are at least 1,000-base-pair differences between individual people, and have been linked to both benign and disease-causing changes in the human genome.

Analysis of DNA from ancient individuals of the Near East documents the extreme substructure among the populations which transitioned to farming, a structure that was maintained throughout the transition from hunter–gatherer to farmer but that broke down over the next five thousand years.

Quasicrystals show long-range order but lack the symmetry of conventional crystals. Here, the authors study the bulk electronic structure of quasicrystals and their three-dimensional Fermi surface topology, providing links to the structural stability of these materials.

Advances in DNA-sequencing technology provide unprecedented insight into the entire collection of four genomes' transcribed sequences. They herald a new era in the study of gene regulation and genome function.

Analyses of epigenomic datasets spanning transitions from normal prostate epithelium to localized prostate cancer to metastases show that latent developmental programs are reactivated in metastatic disease and that prostate lineage-specific regulatory elements are strongly enriched for prostate cancer risk heritability.

Photolithography is an established microfabrication technique but commonly uses costly shortwavelength light sources to achieve high resolution. Here the authors use metal patterns embedded in a flexible elastomer photomask with mechanical robustness for generation of subdiffraction patterns as a cost effective near-field optical printing approach.

A two-photon computed tomography approach, called scanned line angular projection microscopy, enables high-speed imaging at over 1 kHz frame rates, as demonstrated for glutamate imaging in the in vivo mouse brain.

Condensates composed of the disordered region of the mediator of RNA polymerase II transcription subunit 1 (MED1) are known to partition specific proteins, but whether this specificity arises from ordered-structure-mediated or dynamic multivalent amino acid interactions remains unclear. Here, the authors show that a physics-based model that only accounts for multivalent polymer interactions is able to explain and predict selective partitioning, suggesting that the specificity of condensate composition is underpinned by multivalent interactions in the context of conformational disorder.

Lipson et al. profile the yeast transcriptome using single-molecule sequencing. This approach avoids the inherent biases of the digestion, ligation and amplification steps in alternative methods based on microarrays or other sequencing technologies.

The open-source FALCON and FALCON-Unzip software utilize long-read sequencing data to generate contiguous, accurate and phased diploid assemblies, even from genomes that are highly heterozygous.

The genome of Ectocarpus siliculosis, a model for the study of brown algae, has been sequenced. These seaweeds are complex photosynthetic organisms that have adapted to rocky coastal environments. Genome analysis sheds light on this adaptation, revealing an extended set of light-harvesting and pigment biosynthesis genes, and new metabolic processes such as halide metabolism. Comparative analyses are also significant with respect to the evolution of multicellularity in plants, animals and brown algae.

This study tracked the initial self-assembly, oligomerization and structural conversion of α-synuclein inside neurons. Early seeding events occur on mitochondrial membranes, where oligomerization induces mitochondrial dysfunction and neuronal loss.

Local activity of the DNA methylation machinery remains poorly understood. Here, the authors present a theoretical and experimental framework to infer methylation and demethylation rates at genome scale in mouse embryonic stem cells, finding that maintenance methylation activity is reduced at transcription factor binding sites, while methylation turnover is elevated in transcribed gene bodies.

Hydrogels incorporating human stromal cells and that after implantation in mice recruit cells from an orthotopic human tumour xenograft enable, after the injection of human immune cells, the study of the evolution of pre-metastatic niches.

In the absence of progranulin, microglia enter a disease-specific state that causes endolysosomal dysfunction and neurodegeneration, and these microglia promote TDP-43 granule formation, nuclear pore defects and cell death specifically in excitatory neurons via the complement activation pathway.

Despite major drug discovery efforts, the therapeutic options for glioblastoma (GBM) remain inadequate. Here they analyze patient-derived xenograft model of GBM to quantitatively map distribution and cellular response to the EGFR inhibitor erlotinib, and report heterogeneous erlotinib delivery to intracranial tumors to be inadequate to inhibit EGFR signaling.

Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

In chronic lymphocytic leukemia (CLL), evolution is driven by transcriptional and epigenetic heterogeneity. Here, the authors integrate epigenomic analyses to show how intra-tumoral epigenetic diversity results in divergent chromatin states in CLL cells, increasing cell-to-cell transcriptional heterogeneity.

In real-world spatial navigation and observation tasks, oscillatory activity in the human brain encodes representations of self and others, with oscillatory power increasing at locations near the boundaries of the room.

Solutions of computations can be encoded in the ground state of many-body spin models. Here the authors show that solutions to generic reversible classical computations can be encoded in the ground state of a vertex model, which can be reached without finite temperature phase transitions.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Systems level analysis finds two transcription factors, Rv0324 and Rv0880, are required for Mycobacterium tuberculosis tolerance to bedaquiline.

Copy number variants (CNVs) account for a major proportion of human genetic diversity and may contribute to genetic susceptibility to disease. Here, a large, genome-wide study of association between common CNVs and eight common human diseases is presented. The study provides a wealth of technical insights that will inform future study design and analysis. The results also indicate that common CNVs that can be 'typed' on existing platforms are unlikely to contribute much to the genetic basis of common diseases.

Application of next-generation sequencing using the ABI SOLiD technology to mammalian transcriptome analysis enabled a survey of the content, the complexity and the developmental dynamics of the embryonic stem cell transcriptome in the mouse. Also in this issue, Mortazavi et al. report Illumina technology–based RNA-Seq analysis of the mouse transcriptome in three different tissues.

A combination of genetic tricks and fancy fluorescent proteins is used to develop the Technicolor version of Golgi staining, 'Brainbow', in which hundreds of individual neurons are painted, each with a distinctive hue. This technology should not only boost mapping efforts in normal or diseased brains, but could also be applied to other complex cell populations, such as the immune system.

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

Assembly of haplotype-resolved human genomes is achieved by combining short and long reads.

Studies of the functional organization of the prefrontal cortex have produced contradicting results depending on the task used. Here, Riley and colleagues demonstrate that prefrontal areas are specialized across the anterior posterior axis and that the effects of the task themselves impact more the anterior areas.

The most abundant RNA modification in humans, m⁶A, can be installed at specified RNA sequences in cells, enabling functional studies.

Fe₃Sn₂ hosts massive Dirac fermions, owing to the underlying symmetry properties of the bilayer kagome lattice in the ferromagnetic state and the atomic spin–orbit coupling.

In this study, the authors show that the spatial responses of populations of grid cells are constrained to a two-dimensional activity manifold, and the relationships between pairs of grid cells are resistant to perturbation. These findings provide evidence of low-dimensional continuous attractor dynamics in the network.

Immature poxviruses are characterized by nonicosahedral semiordered protein scaffolds critical for morphogenesis. Here, the authors use cryo-EM structures of Vaccinia virus D13 scaffold intermediates to explain their assembly mechanism.

Rearrangements of the Ig loci are essential for generating antibody diversity but abnormal translocations can be a driving event for myeloma. Here Walker et al. perform whole exome sequencing on myeloma patients to capture the diversity of mutational changes.

Artificially engineered tissues may be useful for regenerative therapies but their fabrication tends to be complicated. Stevens et al. present a technique for the precise organization of microstructurally complex tissues that works with a variety of cell types and does not require sophisticated equipment.